The biological properties of oncolytic viruses, in particular the ability to replicate within a tumor cell and then spread from cell to cell are highly desirable features for cancer therapy. However. several features of the tumor environment may not be conducive for efficient viral spread. Hypoxia is an important feature of solid tumors and the ability of viruses to replicate in hypoxic conditions may be a critical determinant in the success or failure of virotherapy. Turning off protein translation is a central process in the cellular adaptation to many types of stress, including viral infection and hypoxia. How a specific virus has evolved to overcome the cellular mechanisms that regulate translation in the cell under stress may be critical for the success of virotherapy.